This project is designed to further develop and facilitate collaborative research on age-related cognitive loss at the TN Medical College/Nair Hospital in Mumbai (Bombay) India, working in conjunction with the Mount Sinai Alzheimer's Disease Research Center (ADRC). This collaboration was initiated through support of an R21 Developmental Grant under the Brain Disorders in the Developing World: Research Across the Lifespan initiative. We now propose a more extensive RO1 grant to further develop the capabilities of our Indian colleagues to carry out research clinical evaluations and longitudinal assessments of cognitive function in the elderly as well as the preparation of postmortem brain specimens for neuropathologic diagnosis and brain banking. Epidemiologic studies of elderly Indian populations indicate that prevalence rates for Alzheimer's are dramatically lower than are seen in the developed nations. In this project, we will enroll, clinically assess, diagnose and longitudinally follow a cohort of 150 elderly individuals from Mumbai with mild to moderate cognitive impairment as well as a comparative group of 100 normal elderly controls. In addition, we will develop a facility for performing neuropathologic characterization and diagnostic evaluation of clinically evaluated subjects who come to autopsy during the course of the study. In doing this we will characterize the clinical features, natural history and neuropathologic correlates of cognitive loss among the urban elderly inhabitants of Mumbai. Finally, we will collect brain specimens from 120 elderly subjects from Mumbai who come to autopsy and are free of cognitive impairment (based on a postmortem Clinical Dementia Rating Score or CDR of 0). These brains will be compared with an age-matched series of brains obtained from the Mount Sinai Brain Bank collection (CDR=0) for the extent and distribution of neurofibrillary tangles and beta- amyloid deposits in the form of senile plaques, diffuse plaques and vascular amyloid accumulations. In this way, we will determine if, as our preliminary data suggest, in the course of normal aging the inhabitants of Mumbai show a decreased tendency to develop these cardinal neuropathologic features of Alzheimer's disease. In carrying out this project it is our overall objective to develop a center of expertise in research on age-related cognitive loss in Mumbai. The methodology we propose is patterned on that of the Clinical, Neuropathology, Database, and Education and Information Transfer Cores of the Mount Sinai ADRC, an established, effective and highly productive NIA-funded ADRC.